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Review
. 2021 Nov 19:12:750346.
doi: 10.3389/fimmu.2021.750346. eCollection 2021.

Immune Dysregulation and Infectious Complications in MPN Patients Treated With JAK Inhibitors

Daniele Cattaneo  1   2 , Alessandra Iurlo  1
Affiliations
Review

Immune Dysregulation and Infectious Complications in MPN Patients Treated With JAK Inhibitors

Daniele Cattaneo et al. Front Immunol. .

Abstract

BCR-ABL1-negative myeloproliferative neoplasms are burdened by a reduced life expectancy mostly due to an increased risk of thrombo-hemorrhagic events, fibrotic progression/leukemic evolution, and infectious complications. In these clonal myeloid malignancies, JAK2V617F is the main driver mutation, leading to an aberrant activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Therefore, its inhibition represents an attractive therapeutic strategy for these disorders. Several JAK inhibitors have entered clinical trials, including ruxolitinib, the first JAK1/2 inhibitor to become commercially available for the treatment of myelofibrosis and polycythemia vera. Due to interference with the JAK-STAT pathway, JAK inhibitors affect several components of the innate and adaptive immune systems such as dendritic cells, natural killer cells, T helper cells, and regulatory T cells. Therefore, even though the clinical use of these drugs in MPN patients has led to a dramatic improvement of symptoms control, organ involvement, and quality of life, JAK inhibitors-related loss of function in JAK-STAT signaling pathway can be a cause of different adverse events, including those related to a condition of immune suppression or deficiency. This review article will provide a comprehensive overview of the current knowledge on JAK inhibitors' effects on immune cells as well as their clinical consequences, particularly with regards to infectious complications.

Keywords: JAK inhibitors; immune system; infections; myeloproliferative neoplasms; ruxolitinib.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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